Chemical synthesis, structural analysis, and decomposition of N-nitroso bile acid conjugates

Article abstract of DOI:10.1016/0968-0896(96)00084-3

N-nitrosoamides of 7β-hydroxylated bile acid conjugates, particularly of the ursodeoxycholic acid family have been synthesized. The products and synthetic intermediates were fully characterized by the results of high- resolution ¹H NMR, FT-1R, FABMS and ESI-MS studies. The compounds, N- nitrosoglycoursodeoxycholic acid (NOGUDCA), N-nitrosoglycoursocholic acid (NOGUCA) and N-nitrosoglycodeoxycholic acid (NOGDCA) decomposed between pH 6 and 9 in aqueous bullet solutions, indicating a t( 1/2 ) of 5-7 h while N- nitrosotauroursodeoxycholic acid (NOTUDCA) indicated a much longer t( 1/2 ) of 15-17 h. These results suggest that the compounds are relatively stable and may enter the enterohepatic circulation. Their decomposition is similar to that of other N-nitrosamides, which generate alkylating agents and thereby act as DNA mutagens.